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Biomedical subjects

L Cinotti

Publications and source records attributed to L Cinotti.

At least 19 recordsLinked to original sources

Extraction of epileptogenic foci from PET and SPECT images by fuzzy modeling and data fusion.

During the presurgical evaluation of medically intractable epilepsy, isotopic functional imagery provides an increasing amount of data concerning the potential location of the focus. The aim of this study is to facilitate the surgical decision by presenting an image fusion method able to extract epileptogenic foci from periictal single photon emission computed tomography (SPECT), interictal SPECT, fluoro-desoxy-glucose (FDG) position emission tomography (PET), and flumazenil PET. After spatial coregistration, the images are converted into fuzzy maps whose membership functions indicate the pathological degree of each voxel, according to each modality. These maps are then fused together thanks to a combination operator managing uncertainty (due to the sensitivity) and imprecision (due to poor resolution and partial volume effect) of the images. In the framework of possibilistic theory, this operator mimics the way the physicians evaluate and compare the various exams. The technique was successfully tested on simulated images with well-defined abnormalities, in terms of size and intensity. A preliminary clinical study was also performed and gave results in accordance with the "gold standard" investigation (deep electrodes or postsurgical outcome) in 11 patients out of 12.

Adult↗

Brain processing of visual sexual stimuli in human males.

Despite its critical sociobiological importance, the brain processing of visual sexual stimuli has not been characterized precisely in human beings. We used Positron Emission Tomography (PET) to investigate responses of regional cerebral blood flow (rCBF) in nine healthy males presented with visual sexual stimuli of graded intensity. Statistical Parametric Mapping was used to locate brain regions whose activation was associated with the presentation of the sexual stimuli and was correlated with markers of sexual arousal. The claustrum, a region whose function had been unclear, displayed one of the highest activations. Additionally, activations were recorded in paralimbic areas (anterior cingulate gyrus, orbito-frontal cortex), in the striatum (head of caudate nucleus, putamen), and in the posterior hypothalamus. By contrast, decreased rCBF was observed in several temporal areas. Based on these results, we propose a model of the brain processes mediating the cognitive, emotional, motivational, and autonomic components of human male sexual arousal.

Adult↗

Towards an optimal reference region in single-photon emission tomography difference images in epilepsy.

There is marked variability in the cerebral blood flow (CBF) between the ictal and interictal state in epilepsy, and it would therefore be desirable to increase the reliability of ictal/interictal single-photon emission tomography (SPET) difference images. We aimed to improve the step of quantitative normalization of images by finding the best possible reference region. In 16 patients (11 with lateralization of the epileptogenic focus, five with bilateral foci) both ictal and inter-ictal SPET scans were performed after injection of technetium-99m labelled tracer. Then, each region among a selected set (brain+cerebellum, brain, cerebellum, hemispheres, and for patients with an expected lateralization, cortical lobe containing the focus and symmetrical contralateral lobe) was investigated by comparison of the regional ictal/inter-ictal variance in counts. Among patients with a suspected lateralized focus, the distribution of CBF in the contralateral cortical lobe appeared to vary less between ictal and inter-ictal states than in other investigated areas. As a consequence, this latter region constitutes the best choice as a reference region. For patients with bilateral foci, the cerebellum appears to be a good compromise even though it presents with significant CBF changes.

Brain↗

Renal blood flow measurement by positron emission tomography using 15O-labeled water.

BACKGROUND: Only few noninvasive methods have the potential to quantitate renal blood flow (RBF) in humans. Positron emission tomography (PET) is a clinical imaging method that can be used to measure the tissue blood flow noninvasively. The purpose of this study was to validate PET measurement of RBF using 15O-labeled water (H215O), a tracer that allows repeated measurements at short time intervals. METHODS: RBF was measured in six pigs by PET and by radioactive microspheres (MS). Three measurements were performed in each pig at baseline (BL), during vascular expansion and dopamine infusion (DA; 20 microg. kg-1. min-1 intravenously), and during angiotensin II (Ang II) infusion (50 ng. kg-1. min-1 intravenously). RBF was estimated from aortic and renal tracer kinetics using a model adapted from the blood flow model described by Kety and Smith. RESULTS: PET and MS values correlated strongly (y = 0.79x + 42, r = 0.93, P < 0.0001) over the RBF range from 100 to 500 mL. min-1. 100 g-1. Pharmacologically induced changes were significant and were measured equally well by PET and MS: 38 and 39%, respectively, below BL (P < 0.005 and P < 0.05) under Ang II, and 47 and 48%, respectively, above BL (P < 0.005 and P < 0.01) under DA. A Bland and Altman representation showed a low average difference of -17 +/- 45 mL. min-1. 100 g-1 (mean +/- SD). CONCLUSION: To our knowledge, this study provides the first validation of RBF measurement by PET using H215O over a large range of RBF values (100 to 500 mL. min-1. 100 g-1), which correspond to RBF values in both healthy subjects and in patients suffering from chronic renal failure.

Animals↗

[18F]fluorodeoxyglucose positron emission tomography in the diagnosis of cancer in patients with paraneoplastic neurological syndrome and anti-Hu antibodies.

The diagnosis of cancer is often difficult in patients with paraneoplastic neurological syndrome and anti-Hu antibodies. Fluorodeoxyglucose 18 positron emission tomography scanning is a highly sensitive and specific method to detect lung tumors. We investigated 15 patients with paraneoplastic neurological syndrome and anti-Hu antibodies. Radiological methods led to the diagnosis of cancer in 12 patients, and test results were negative in 3. Whole-body [18F]fluorodeoxyglucose positron emission tomography showed abnormal uptake in the mediastinum in these 3 patients in accordance with the expected location of the malignancy.

Aged↗

Neuroanatomical correlates of visually evoked sexual arousal in human males.

Brain areas activated in human male sexual behavior have not been characterized precisely. For the first time, positron emission tomography (PET) was used to identify the brain areas activated in healthy males experiencing visually evoked sexual arousal. Eight male subjects underwent six measurements of regional brain activity following the administration of [15O]H2O as they viewed three categories of film clips: sexually explicit clips, emotionally neutral control clips, and humorous control clips inducing positive but nonsexual emotions. Statistical Parametric Mapping was used to identify brain regions demonstrating an increased activity associated with the sexual response to the visual stimulus. Visually evoked sexual arousal was characterized by a threefold pattern of activation: the bilateral activation of the inferior temporal cortex, a visual association area; the activation of the right insula and right inferior frontal cortex, which are two paralimbic areas relating highly processed sensory information with motivational states; and the activation of the left anterior cingulate cortex, another paralimbic area known to control autonomic and neuroendocrine functions. Activation of some of these areas was positively correlated with plasma testosterone levels. Although this study should be considered preliminary, it identified brain regions whose activation was correlated with visually evoked sexual arousal in males.

Adult↗

Functional anatomy of perceptual and semantic processing for odors.

The functional anatomy of perceptual and semantic processings for odors was studied using positron emission tomography (PET). The first experiment was a pretest in which 71 normal subjects were asked to rate 185 odorants in terms of intensity, familiarity, hedonicity, and comestibility and to name the odorants. This pretest was necessary to select the most appropriate stimuli for the different cognitive tasks of the second experiment. The second one was a PET experiment in which 15 normal subjects were scanned using the water bolus method to measure regional cerebral blood flow (rCBF) during the performance in three conditions. In the first (perceptual) condition, subjects were asked to judge whether an odor was familiar or not. In the second (semantic) condition, subjects had to decide whether an odor corresponded to a comestible item or not. In the third (detection) condition, subjects had to judge whether the perceived stimulus was made of an odor or was just air. It was hypothetized that the three tasks were hierarchically organized from a superficial detection level to a deep semantic level. Odorants were presented with an air-flow olfactometer, which allowed the stimulations to be synchronized with breathing. Subtraction of activation images obtained between familiarity and control judgments revealed that familiarity judgments were mainly associated with the activity of the right orbito-frontal area, the subcallosal gyrus, the left inferior frontal gyrus, the left superior frontal gyrus, and the anterior cingulate (Brodmann's areas 11, 25, 47, 9, and 32, respectively). The comestibility minus familiarity comparison showed that comestibility judgments selectively activated the primary visual areas. In contrast, a decrease in rCBF was observed in these same visual areas for familiarity judgments and in the orbito-frontal area for comestibility judgments. These results suggest that orbito-frontal and visual regions interact in odor processing in a complementary way, depending on the task requirements.

Adult↗

Paradoxical metabolic response of the human brain to a single electroconvulsive shock.

Regional brain protein synthesis was evaluated with positron emission tomography (PET) and L-(S-[11C]methyl)methionine ([11C]MET) in depressive patients, before and 3 h after an electroconvulsive shock (ECS), when energy supply is restored, and in healthy volunteers. Depressive patients presented apparent lower protein synthesis than normals, in agreement with known reduction of cerebral activity. In contrast, ECS resulted in a significant increase (56%, P < 0.05) in global cortical protein synthesis. This paradoxical hyperactivation of cellular protein metabolism in response to seizures and the fact that synaptic activity is further reduced after electroconvulsive therapy (ECT), may provide new insights for understanding the mechanism of action of ECT.

Adult↗

Can cerebrovascular reactivity be assessed by dynamic susceptibility contrast-enhanced MRI?

The acetazolamide (ACZ) test is performed to evaluate the decrease in cerebral perfusion pressure (CPP) by investigation of vasomotor reactivity (VMR). Our aim was to study cerebral blood flow and blood volume changes induced by the ACZ test in healthy control subjects using dynamic susceptibility contrast-enhanced gradient-echo MRI (DSC-MRI). A FLASH sequence was used to produce susceptibility-weighted images during an intravenous injection of 0.1 mmol/kg gadopentetate dimeglumine (Gd-DTPA). After the first dynamic study, 1 g acetazolamide was given intravenously and 10 min later a second bolus of Gd-DTPA was injected. Using the indicator-dilution theory, relative cerebral blood volume and relative cerebral blood flow were estimated. In healthy subjects the ACZ test induced a significant increase in relative blood volume (from 80.5 +/- 10.7 to 113.4 +/- 11.9) and relative blood flow (from 5.73 +/- 0.96 to 7.5 +/- 0.97), symmetrically in the cerebral hemispheres. This approach might be promising in the understanding of cerebral haemodynamics in patients with vascular disorders.

Acetazolamide↗

Metabolic myocardial viability assessment with iodine 123-16-iodo-3-methylhexadecanoic acid in recent myocardial infarction: comparison with thallium-201 and fluorine-18 fluorodeoxyglucose.

The best test presently available to ascertain residual viability within an infarct-related area involves the use of fluorine-18 fluorodeoxyglucose (FDG) to detect the persistence of some cellular metabolism. Rest reinjection of thallium-201 is a less accurate alternative but is easy to perform. Iodinated fatty acids, which are used with standard gamma cameras, are proposed as markers of cellular metabolism. This study was performed to assess the value of 16-iodo-3-methylhexadecanoic acid (MIHA) as a marker of the residual cellular metabolism by comparison with FDG in patients with a recent myocardial infarction, and to evaluate its contribution compared with the 201Tl stress-redistribution-reinjection technique. Stress-redistribution-reinjection 201Tl imaging, rest MIHA imaging and glucose-loaded FDG imaging were performed in 22 patients with recent myocardial infarction. Out of the 628 myocardial segments obtained from the left ventricular analysis, 400 were hypoperfused (relative uptake <0.75 of maximum uptake on stress 201Tl imaging), 177 of which were severely hypoperfused (relative uptake <0.50). Receiver operating characteristic (ROC) curves for predicting metabolic myocardial viability with FDG were derived from the results in respect of (a) 201Tl activity during exercise, redistribution and reinjection and (b) MIHA uptake, using the two FDG thresholds most commonly considered to define metabolic viability (0.50 and 0.60). Analysis of the 400 hypoperfused segments demonstrated that 201Tl reinjection was the most accurate test in predicting the presence of myocardial viability (area under the ROI curves=0.85 and 0.86 at the 0.50 and 0.60 FDG thresholds, respectively; P<0.05 vs other tests). The global predictive values of MIHA and 201Tl reinjection were, respectively, 0.87 and 0.89 at the 0.50 FDG threshold (NS), and 0.82 and 0.87 at the 0.60 FDG threshold (NS). When only the 177 severely hypoperfused segments were considered, 201Tl reinjection remained the most accurate test (accuracy 0.84 at the 0.50 FDG threshold and 0.82 at the 0.60 FDG threshold), while the accuracy of MIHA decreased significantly (0.78 at the 0.50 FDG threshold and 0.73 at the 0.60 FDG threshold, P<0.05 vs 201Tl reinjection). In all circumstances, MIHA was less specific than 201Tl reinjection for the detection of metabolic viability. In conclusion, in patients with recent myocardial infarction, MIHA accurately detects the persistence of metabolic viability, but is not superior to 201Tl.

Deoxyglucose↗

Assessment of cerebrovascular reactivity by dynamic susceptibility contrast-enhanced MR imaging.

In patients with cerebrovascular disease the acetazolamide (ACZ) test is performed to evaluate the decrease in cerebral perfusion pressure (CPP) through the investigation of the vasomotor reactivity (VMR). This latter is currently assessed with ACZ with several methods. Recently, magnetic resonance imaging (MRI) techniques have been developed that are sensitive to stimulus-induced changes in blood flow. Dynamic susceptibility contrast material-enhanced gradient-echo MRI techniques (DSC-MRI) might be an attractive tool to assess VMR. We aimed to test the ability of DSC-MRI in the assessment of VMR. Relative hemodynamic parameters rCBV, MTT, and rCBF were evaluated at baseline after the first injection of gadopentetate dimeglumine and 10 min after the intravenous administration of ACZ (1 g) with a second bolus of contrast agent. Assessment of hemodynamic parameters was performed over the whole hemisphere and also within regions of interest. The significances of the mean differences, before and after ACZ, were assessed with repeated-measures ANOVA with two within factors: laterality (right-left) and ACZ. DSC-MRI with ACZ test was performed in ten healthy controls (aged 51.4+/-16.2 years). The cerebral hemispheric ratio for the three parameters (cerebral blood volume (CBV), mean transit time (MTT), and cerebral blood flow (CBF)) ranged between 1.01 and 1.03. The mean gray matter-to-white matter ratio for CBV, CBF and MTT were 2.44, 2.41 and 1.05, respectively. As the laterality effect was not significant, left and right hemispheric values were averaged. A significant increase of all hemodynamic parameters was observed after ACZ (P<0.01-0.001). The same changes for CBV, CBF and MTT were observed after ACZ according to the regions of interest (P<0.006-0.015). DSC-MRI is a non-invasive method which enables the assessment of VMR. This technique may be added to any conventional MRI in order to detect a hemodynamic impact of an ICA stenosis. Therefore, it might be useful in determining the appropriate management when the indication for surgical versus medical therapy is in question.

Acetazolamide↗

Brain glucose metabolism with [18F]-fluorodeoxyglucose and positron emission tomography before and after surgical resection of epileptogenic cavernous angiomas.

Surgery of cavernous angiomas is often proposed due to the epileptogenic and hemorrhagic potential of this lesion. Little information is available on the impact of surgical resection on brain metabolism, locally or at a distance from the lesion. Fifteen patients presenting with a cavernoma and epileptic seizures underwent positron emission tomography examinations before and 1 year after surgical resection. We studied the quantitative cerebral metabolic rate of glucose (CMRGlu) with [18F]-fluorodeoxyglucose. The global brain CMRGlu remained unchanged after surgery. There was a significant decrease of metabolism in the lesion hemisphere, which remained unchanged after surgery. The perilesional regions were less metabolic than the contralateral ones and less metabolic than remote regions within the same hemisphere, before and after surgery. The absence of pre- to postsurgical variations suggests that the metabolic consequences of the lesion are maintained despite the surgical procedure during long-term follow-up studies.

Brain↗

A controlled positron emission tomography study of obsessive and neutral auditory stimulation in obsessive-compulsive disorder with checking rituals.

Ten nondepressed patients with obsessive-compulsive disorder (OCD) who were characterized by predominant checking rituals were compared with 10 age- and sex-matched control subjects. Hemispheric and regional cerebral blood flow levels (rCBF) were measured with positron emission tomography (H2 15O) across four conditions: rest, auditory stimulation with idiosyncratic normal or abnormal obsession, auditory stimulation with neutral verbal stimuli, and rest. Order of neutral and obsessive stimulation was randomized. Higher subjective responses to obsessive than to neutral stimulation were found in both groups; subjective response was higher in OCD patients when obsessive stimulation was presented first. A four-way analysis of variance (group x stimulation order x hemisphere x condition [neutral or obsessive stimulation]) was performed on stimulation minus rest normalized rCBF values. Control subjects had significantly higher rCBF in the thalamus and putamen. A trend toward higher rCBF in OCD patients was found in the superior temporal regions. When neutral stimulation was presented first, rCBF was significantly higher in the caudate region of control subjects. Obsessive stimulation was associated with higher rCBF than neutral stimulation in orbitofrontal regions in both groups of subjects. Under obsessive stimulation, superior temporal and orbitofrontal activities were correlated in OCD patients but not in control subjects. Our study suggests specific abnormalities of information processing in the basal ganglia and temporal structures of compulsive checkers.

Adult↗

Slowly progressive anarthria with late anterior opercular syndrome: a variant form of frontal cortical atrophy syndromes.

We describe eight patients with slowly progressive speech production deficit combining speech apraxia, dysarthria, dysprosody and orofacial apraxia, and initially no other deficit in other language and non-language neuropsychological domains. Long-term follow-up (6-10 years) in 4 cases showed an evolution to muteness, bilateral suprabulbar paresis with automatic-voluntary dissociation and frontal lobe cognitive slowing without generalised intellectual deterioration. Most disabled patients presented with an anterior opercular syndrome (Foix-Chavany-Marie syndrome), and pyramidal or extrapyramidal signs. CT and MRI findings disclosed asymmetric (left > right) progressive cortical atrophy of the frontal lobes predominating in the posterior inferior frontal region, notably the operculum. SPECT and PET revealed a decreased cerebral blood flow and metabolism, prominent in the left posterior-inferior frontal gyrus and premotor cortex, extending bilaterally in the most advanced cases. Pathological study of two cases showed non-specific neuronal loss, gliosis, and spongiosis of superficial cortical layers, mainly confined to the frontal lobes, with no significant abnormalities in the basal ganglia, thalamus, cerebellum, brain stem (except severe neuronal loss in the substantia nigra in one case), and spinal cord. We propose to call this peculiar syndrome Slowly Progressive Anarthria (SPA), based on its specific clinical presentation, and its metabolic and pathological correlates. SPA represents another clinical expression of focal cortical degeneration syndromes, that may overlap with other similar syndromes, specially primary progressive aphasia and the various frontal lobe dementias.

Aged↗

Error analysis on parameter estimates in the ligand-receptor model: application to parameter imaging using PET data.

Positron emission tomography and compartmental models allow the in vivo analysis of radioligand binding to receptor sites in the human brain. Benzodiazepine receptor binding was studied using a three-compartmental model and [11C]flumazenil. Four and five parameters were estimated from a single kinetic curve obtained with a multi-injection protocol, and parametric maps of receptor density and of the individual kinetic parameters were created with four-pixel sampling of the experimental images. The coefficient of variation on each estimated model parameter was calculated using the diagonal elements of the covariance matrix. However, these estimates are valid only under some statistical hypotheses which are not always verified with PET data. Thus, in order to verify the validity of the coefficient of variation of each parameter calculated with the covariance matrix, these results have been compared with the more rigorous statistical results provided by a Monte Carlo simulation. The study showed a negligible difference between the results obtained by the two methods for a low noise level in time-concentration curves encountered using large ROIs. However, this bias becomes less negligible when the noise level is high and some estimations of the coefficients of variation were unacceptable (> 100%) with the five-parameter model. Such difficulties did not occur with the four-parameter model which led to parametric images with good quality and acceptable estimates of coefficients of variation (less than 20% in about 75% of the ROIs).

Brain↗

Positron emission tomography metabolic data corrected for cortical atrophy using magnetic resonance imaging.

The correct interpretation of clinical positron emission tomography (PET) data depends largely on the physical limits of the PET scanner. The partial volume effect (PVE) is related to the size of the studied object compared to the spatial resolution. It represents one of the most important limiting factors in quantitative data analysis. This effect is increased in the case of atrophy, as in patients with Alzheimer disease (AD), and it influences measurement of the metabolic reduction generally seen in cerebral degeneration. In this case, interpretation can be biased, because cortical activity will be underestimated due to the atrophy. In general, anatomical images of AD patients have shown diffuse atrophy, while PET studies have found widespread hypometabolism affecting the parietal and temporal lobes. Although hypometabolic areas usually correspond to atrophic regions, they also occur without such changes. Thus, the aim is to differentiate authentic hypometabolism (decrease of glucose consumption per unit volume of gray matter) from that due to PVE from atrophy (cell loss). Consequently, we are using a method for three-dimensional (3D) correction of human PET data with 3D magnetic resonance imaging (MRI). We measured atrophy and metabolism by using both T1-weighted MR images and high and medium resolution PET scans. We injected 12 patients and controls with [18F]fluorodeoxyglucose for glucose consumption measurements. Atrophy was estimated in the following way. We isolated the cerebral structures, using a segmentation technique on the MRI scans, into gray matter (GM), white matter, and cerebrospinal fluid. We superimposed the PET images onto the MR images to obtain anatomo-functional correlations. We degraded the segmented MR images to the resolution of the PET images by a convolution process to create a PET image correction map. We corrected the metabolic PET data for the PVE. We studied the cerebral metabolic rate of glucose in the GM where metabolic variation is the most relevant to AD. By dealing with problems relating to the sensitivity to the segmentation and to the PET-MRI coregistration, computation of MRI convolution processes provided the degree of PVE on a pixel-by-pixel basis, allowing correction of hypometabolisms contained in GM PET values. Global cortical metabolism increased after correction for PVE by, on average, 29 and 24% for tomographs acquired with medium (TTV03 LETI) and high (ECAT 953B CTI/Siemens) resolution, respectively, whereas the cortical metabolism increased by 75 and 65% for the respective tomographs in AD patients. The difference of metabolism between scans after correction for PVE was less than before correction, decreasing from 31 to 17%. This difference was most marked in the frontal and temporal lobes. Fusion imaging allowed correction for PVE in metabolic data using 3D MRI and determination of whether a change in the apparent radiotracer concentration in PET data reflected an alteration in GM volume, a change in radiotracer concentration per unit volume of GM, or both.

Adult↗

Perfusion-MVO2 mismatch during inotropic stress in CAD patients with normal contractile function.

With the use of[11C]acetate, positron emission tomography (PET) permits exploration of myocardial blood flow (MBF) and oxidative metabolism (MVo2) coupling. PET imaging was performed at rest and under dobutamine infusion in 8 normal subjects and 10 coronary artery disease (CAD) patients with significant single-vessel left anterior descending (LAD) stenosis (> 70%) and normal regional left contractile function at rest. Resting MBF and MVo2 were similar in remote and LAD regions of normal subjects and patients. During dobutamine infusion, MBF and myocardial flow reserve were lower in LAD regions of patients compared with remote regions (MBF: 1.49 +/- 0.42 and 2.06 +/- 0.57 ml.g-1.min-1, P < 0.01; reserve: 1.73 +/- 0.59 and 2.14 +/- 0.47, P < 0.01, respectively), whereas MVo2 expressed as kmono (an index of MVo2) and metabolic reserve were similar (kmono: 0.106 +/- 0.021 vs. 0.107 +/- 0.017 min-1; reserve: 1.88 +/- 0.32 vs. 1.98 +/- 0.37, respectively). This is the first human study showing that, in normal contractile regions at rest but perfused by stenosed artery, a disparate rise in MVo2 relative to the rise in myocardial perfusion occurs during increased cardiac work induced by dobutamine. This flow-metabolism uncoupling probably reflects an increase in O2 extraction.

Adult↗